Variant chr2-230327288-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_138402.6(SP140L):c.19G>C(p.Asp7His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000316 in 1,611,880 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000028 ( 0 hom. )

Consequence

SP140L
NM_138402.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.387

Variant links:

Genes affected

SP140L (HGNC:25105): (SP140 nuclear body protein like) Predicted to enable DNA-binding transcription factor activity, RNA polymerase II-specific. Predicted to be involved in regulation of transcription by RNA polymerase II. Predicted to be located in nuclear body. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

SP140L links:

SP140L (HGNC:):

SP140L links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.018598229).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SP140L	NM_138402.6 linkuse as main transcript	c.19G>C	p.Asp7His	missense_variant	1/19	ENST00000415673.7	NP_612411.4	Q9H930-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
SP140L	ENST00000415673.7 linkuse as main transcript	c.19G>C	p.Asp7His	missense_variant	1/19	5	NM_138402.6	ENSP00000397911.2	Q9H930-4
SP140L	ENST00000243810.10 linkuse as main transcript	c.19G>C	p.Asp7His	missense_variant	1/18	1		ENSP00000243810.7	U5Y3L1
SP140L	ENST00000396563.8 linkuse as main transcript	c.19G>C	p.Asp7His	missense_variant	1/17	1		ENSP00000379811.5	H7BYP4
SP140L	ENST00000444636.5 linkuse as main transcript	c.19G>C	p.Asp7His	missense_variant	1/15	5		ENSP00000395195.1	Q9H930-1

Frequencies

GnomAD3 genomes

AF:

0.0000657

AC:

AN:

152140

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000571

AC:

AN:

245260

Hom.:

AF XY:

0.0000603

AC XY:

AN XY:

132774

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000715

Gnomad SAS exome

AF:

0.0000333

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000281

AC:

AN:

1459622

Hom.:

Cov.:

AF XY:

0.0000331

AC XY:

AN XY:

725878

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000681

Gnomad4 SAS exome

AF:

0.0000466

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.0000498

GnomAD4 genome

AF:

0.0000657

AC:

AN:

152258

Hom.:

Cov.:

AF XY:

0.0000806

AC XY:

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000642

ExAC

AF:

0.0000577

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 22, 2023

The c.19G>C (p.D7H) alteration is located in exon 1 (coding exon 1) of the SP140L gene. This alteration results from a G to C substitution at nucleotide position 19, causing the aspartic acid (D) at amino acid position 7 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.43

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.0042

.;T;T;.

Eigen

Benign

-0.52

Eigen_PC

Benign

-0.74

FATHMM_MKL

Benign

0.089

LIST_S2

Benign

0.69

T;T;T;T

M_CAP

Benign

0.012

MetaRNN

Benign

0.019

T;T;T;T

MetaSVM

Benign

-0.48

MutationAssessor

Benign

1.5

L;L;.;.

PrimateAI

Uncertain

0.52

PROVEAN

Benign

-1.1

N;N;N;N

REVEL

Uncertain

0.30

Sift

Benign

0.17

T;T;T;T

Sift4G

Uncertain

0.0040

D;D;D;D

Vest4

0.12

MutPred

0.24

Gain of MoRF binding (P = 0.0333);Gain of MoRF binding (P = 0.0333);Gain of MoRF binding (P = 0.0333);Gain of MoRF binding (P = 0.0333);

MVP

0.65

MPC

0.10

ClinPred

0.098

GERP RS

0.77

Varity_R

0.039

gMVP

0.25

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over